|
REVIEW ARTICLE |
|
| Year : 2010 | Volume
: 55
| Issue : 1 | Page : 3-7 |
|
| Hirsutism: Evaluation and treatment |
|
|
Silonie Sachdeva
Department of Dermatology, Carolena Skin, Laser & Research Centre, Jalandhar - 144022 Punjab, India
| Date of Web Publication | 4-Mar-2010 |
Correspondence Address:
Silonie Sachdeva
1312, Urban Estate, Phase-1, Jalandhar - 144 022, Punjab
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/0019-5154.60342
|
|
 Abstract | | |
Hirsutism is a common clinical condition seen in female patients of all ages. It affects around 5-10% of the women and is a common presenting complaint in the dermatological out patient department for cosmetic reasons. The cause is mainly hyperandrogeneism, which may be ovarian or adrenal. It may be part of a rare metabolic syndrome, drug induced, or just idiopathic. Hirsutism has a huge psychosocial impact, especially in the young females. This article reviews the current evaluation guidelines and management of hirsutism.
Keywords: Hirsutism, evaluation, treatment
How to cite this article:
Sachdeva S. Hirsutism: Evaluation and treatment. Indian J Dermatol 2010;55:3-7 |
| Introduction | |  |
Hirsutism is defined as the presence of terminal coarse hairs in females in a male-like distribution. It affects around 5-10% of women [1],[2] and is a common presenting complaint in the dermatological out patient department (OPD) for cosmetic reasons. It is not only imperative to identify the cause of hirsutism but also important to know how to recommend the right treatment based on the main causative factor. The most important determinant in making the diagnosis is a change in the form and rate of hair growth. A technique has been developed to assess hirsutism with video equipment and computer software. [3] Digital imaging of hair development is recorded, which demonstrates a significant difference in hair form and growth rate between hirsute and non-hirsute women.
Etiology
Classically, hirsutism has been considered a marker of increased androgen levels in females from increased production of androgens (i.e testosterone) either by the adrenals or due to an ovarian disease. [4],[5] The ovarian causes for hyperandrogenism are polycystic ovarian syndrome (PCOS) and ovarian tumors. Adrenal causes include Cushing's syndrome, androgen-producing tumors, and congenital adrenal hyperplasia (CAH), most commonly due to 21-hydroxylase deficiency. Less common causes include the hyperandrogenic-insulin resistant-acanthosis nigricans syndrome (HAIRAN). Hyperprolactinemia by increasing adrenal dihydroepiandrosterone sulfate (DHEA-S) production may cause hirsutism. Androgenic drugs are also an important cause of hirsutism [6] [Figure 1]. About 20% of the patients may present with idiopathic hirsutism (IH) with normal androgen levels and ovarian function. The cause of increased hair in these women is thought to be related to disorders in peripheral androgen activity. [7] Onset of IH occurs shortly after puberty with slow progression. PCOS and IH account for 90% of the hirstutism in women.Hirsutism can also occur in some premenopausal women and continue for a few years after menopause. This is due to decrease in ovarian estrogen secretion with continuous androgen production. [8]
Pathogenesis
Hirsutism is attributed either to increased production or increased sensitivity of the hair follicles to circulating androgen (testosterone, Tst). Majority of Tst is secreted either by the ovaries or adrenals (80%). A small amount of circulating Tst is derived from the conversion of androgenic precursors, mainly androstenedione (derived from the ovaries and adrenals) and dihydroepiandrosterone (DHEA-derived from the adrenals) in liver, skin and adipose tissue. However, only 1-2% of Tst is in free form and is the active androgen. About 98-99% is bound to steroid hormone binding globulin (SHBG), cortisol binding globulin, or nonspecifically to albumin and other proteins and is biologically inactive. Only free Tst is converted to dihydrotestosterone (DHT), by the enzyme 5-alpha reductase type 2 isoenzyme present in the outer root sheath of the hair follicles. [4],[5] This isoenzyme predominates in the testes, prostate, and the hair follicles of beard and genital hair DHT causes terminalisation of the vellus hair and prolongs the anagen phase resulting in longer thicker hairs. IH with normal androgen levels is postulated to result from exaggerated peripheral 5-alpha reductase activity, androgen receptor polymorphisms, or altered androgen metabolism. [7]
Clincal features
Hirsuate women usually present with increased growth of terminal hair at sides of the face, upper lip, chin, upper back, shoulders, sternum, and upper abdomen. Ferriman and Gallwey [2] devised a score for clinical quantification of hirsutism. In their study of 161 women aged 18 to 38 years, they graded density of terminal hair at nine different body sites under androgen effect from 0 (absence of terminal hairs) through 4 (extensive terminal hair growth) and concluded that hirsutism was represented by a score of 8 or more [Figure 2]. However, this is a subjective scale and hence not universally adopted.
Evaluation of hirsute patients
When a female patient presents with the chief complaint of increased growth of hair, it is imperative to see whether the coarse hairs are localized in male distribution or there is generalized increase in growth of the hair on all of the body (hypertrichosis). [9],[10] After determining hirsutism, the follwing steps can be undertaken to find the cause [Figure 1].
- Detailed history incuding age of onset (puberty, middle age, menopause), rate of onset of symptoms (gradual or sudden), any signs or symptoms of virilisation (acne, deepening of voice, infrequent mensturation, loss of breast tissue or loss of normal female body contour, clitoromegaly, increased libido, increased muscle mass as in shoulder girdle, malodorous perspiration etc), history of weight gain or diabetes and drug history prior to onset should be taken.
- Complete general physical and systemic examination should be done including palpation of abdomen for any ovarian mass.
- If drug is the cause, simple withdrawal of the drug should be helpful. For all other cases, laboratory evaluation of the serum markers to know the exact etiology should be done. The various serum markers are-
- Testosterone - Serum testosterone may be normal to increased in case of benign pathology as PCOS and CAH but would be definitely raised (>200 ng/ml) in case of malignant tumor of the adrenal or ovary. [11]
-
Dehydroepiandrosterone sulfate (DHEAS) - Raised DHEAS (>700 µg/dl) always indicates an adrenal cause, benign or malignant.
- 17 Hydroxy progesterone - This serum marker is unique for congenital adrenal hyperplasia. The measurement should be done between 0700 and 0900 hours in the early follicular phase of the menstrual cycle. Levels less than 200 ng/dl excludes the disease. Mildly increased levels between 300 and 1,000 ng/dl require an ACTH stimulation test. Cosyntropin (synthetic ACTH), 250 µg, is administered intravenously, and levels of 17-hydroxyprogesterone are measured before and one hour after the injection. Post-stimulation values (>1,000 ng/dl) constitute a positive test. [11]
- Twenty four hour urine free cortisol should be measured in women with signs and symptoms of Cushing's syndrome.
- LH/FSH greater than 3 is indicative of PCOS. [12]
- Prolactin would be raised in hyperprolactinemia due to hypothalamic disease or a pituitary tumor.
- Serum TSH: Hypophyseal hypothyroidism [13] can act as a cofactor in hirsutism causing raised TSH.
- Pelvic ultrasonography can be done to detect an ovarian neoplasm or a polycystic ovary.
- Magnetic resonance imaging (MRI) or computed tomography (CT) of the adrenal region is useful for diagnosis.
| Treatment | | |
Most women resort to removal of hair by different epilation methods, such as plucking, shaving, and waxing before presenting to the clinic. Though simple and inexpensive, these methods are temporary and have their own side effects like physical discomfort, scarring, folliculitis, irritant dermatitis or discoloration. Electrolysis has also been used for the removal of the hair. With repeated treatments, the efficacy ranges from 15 to 50% permanent hair loss. [14] However, it is difficult to treat large areas like hairs on the chest or upper back with electrolysis and it can be time consuming.
Lasers have gained wide popularity in past two decades and can achieve permanent reduction of hair (not removal). They work on the principle of selective photothermolysis where the laser energy acts specifically to destroy the target (melanin). [15],[16] Laser energy acts on only anagen hair follicles. Therefore, multiple treatment is required to get a significant (i.e. 80%) reduction. An ideal candidate for laser hair removal is a patient with light skin color and dark colored hairs. Different lasers for hair removal include 694-nm ruby laser, the 1064-nm Q-switched Nd: YAG laser, the 755 nm long-pulsed alexandrite, and the 800-nm diode laser. For Indian skin types (Type IV and V), long wavelength lasers like the Nd Yag laser have been found to be most effective. [17] Laser hair removal is most suitable for idiopathic hirsutism with the normal androgen levels.
Treatment with drugs
Before starting medicine, diet and exercise should be advised to all women with PCOS. For all obese women, weight loss as a therapy should be advised. Upper body obesity has been shown to be associated with a reduced sex hormone-binding globulin level and increased free Tst levels in both non-hirsute and hirsute women and can contribute to hirsutism. Drugs are indicated for treatment when hyperandrogenism is confirmed by various laboratory tests. The following drugs can be used:
Oral contraceptives
Oral contraceptives (OCP) are first-line treatment for hirsutism, particularly in those women desiring contraception. Estrogen/progesterone combinations act by-
- reducing gonadotropin secretion and thereby reducing ovarian androgen production. [18]
- increasing levels of SHBG resulting in lower levels of free testosterone.
- inhibiting adrenal androgen production. [19]
Androgen receptor blockers
- Spironolactone (SPA) is an androgen blocker and competes with DHT for binding to the androgen receptor. SPA also has variable progestational activity and decreases production of ovarian androgens. SPA has an inhibitory effect on 5 alpha-reductase activity (5-RA) and competes with androgens for binding to SHBG. The starting dose is 50 mg twice daily and may be increased to a total daily dose of 200 mg. It takes at least six months to have any beneficial effect. The use of SPA is recommended with the OCP which provides adequate contraception and also helps to minimize the dysfunctional uterine bleeding. [19] Side effects include polyuria, and hypotension with associated headaches, fatigue, or even syncope. SPA should not be used in conjunction with other potassium-sparing diuretics, thiazides, in renal insufficiency, or with excess potassium intake, since patients may develop life-threatening hyperkalemia. It is recommended that serum electrolytes and blood pressure be evaluated two to four weeks after treatment is started. Other minor side effects commonly associated with SPA use include gastritis/dyspepsia and dry skin; SPA should be taken with food as this increases its absorption and reduces its potential for gastritis. [20] Absolute contraindications to SPA use include renal insufficiency, anuria, chronic renal impairment, hyperkalemia, pregnancy, and abnormal uterine bleeding.
- Cyproterone Acetate (CA) has strong progestogenic and antiandrogen properties. It produces a decrease in circulating Tst and androstenedione levels through a reduction in circulating LH and has been used as an effective treatment for hirsutism. [21] CPA is available in combination with ethinyl estradiol (EE) (2 mg CPA and 35 µg EE/tablet).
5-RA inhibitors
Finasteride, a 5-alpha reductase inhibtor has been found to be effective in the treatment of IH. [22] Finasteride primarily inhibits type 2 5-RA activity. A 5-RA inhibitor still in clinical testing is dutasteride (GI198745, GlaxoWellcome Co., Research Triangle Park, NC), a "dual" type 1 and type 2 5-RA inhibitor. It is predicted that this drug will be more potent than finasteride. This compound effectively inhibits DHT production by 99% approximately 24 h after oral administration. All these 5-RA agents have the potential of feminizing a male fetus. Hence, effective contraception must be used by patients on these drugs.
Gonadotrophin-releasing hormone (GnRH agonists)
This therapy is parenteral and reserved for women with severe hirsutism who don't respond to the OC and antiandrogens. [23] Long-acting GnRH analogs decrease gonadotrophin secretion and therefore reduce ovarian stimulation and hence testosterone. Estrogen production is also reduced. Hence, therapy is usually used in combination with an oral contraceptive pill containing estrogen and progestin.
Adrenal suppression: Glucocorticoids
The main use of corticosteroids has been to treat hirsutism associated with congenital adrenal hyperplasia (CAH). [24] They are used in a low bedtime dose of dexamethasone. [25]
Biological modifiers of hair follicular growth
Eflornithine hydrochloride is a new agent, which is used as a topical cream (13.9%) for decreasing or arresting facial hair growth in women. It is thought to inhibit hair growth by inhibiting an enzyme involved in keratin synthesis. It is a potent, irreversible inhibitor of the enzyme ornithine decarboxylase, which is necessary for production of the polyamines that mediate cell migration, proliferation, and differentiation. [26] Binding of DHT to the androgen receptor is associated with stimulation of ornithine decarboxylase synthesis and proliferation of hair matrix cells. The cream is applied to the face twice a day. Gradual improvement is seen in six to eight weeks. It can also be used in combination with laser treatments for better effects. [27]
New drugs in trial
A new topical antiandrogen Fluridil (2-hydroxy-2-methyl-N-[4-nitro-3-(trifluoromethyl) phenyl]-3-(2, 2, 2-trifluoroacetylamino)ropanamide) has been developed for hyperandrogenic skin syndromes. [28] Based on these results, a study was conducted as an orientational three-month pilot study to evaluate the efficacy and safety of 2% fluridil gel in female patients with idiopathic hirsutism. The present clinical study has shown that a 2% fluridil gel is a safe and effective treatment method of hirsutism. However, this preparation is not available yet. Compared to systemic administration of antiandrogens, topical fluridil does not affect general health and sexual functions and, more importantly, does not decrease libido.
| Conclusion | | |
Hirustism requires indepth clinical evaluation and investigation for treatment. For pharmacological therapy, oral contraceptives is recommended for the majority of women. Adding an antiandrogen may be needed after six months if the response is suboptimal. Antiandrogen monotherapy is not recommended unless adequate contraception is used. For women who choose hair removal therapy, photoeplilation with lasers is the preferred choice.
| References | | |
| 1. | Mcknight E. The prevalence of "hirsutism" in young women. Lancet 1964;1:410-3.  |
| 2. | Ferriman D, Gallwey JD. Clinical assessment of body hair growth in women. J Clin Endocrinol Metab 1961;21:1440-7 . |
| 3. | Gruber DM, Berger UE, Sator MO, Horak F, Huber JC. Computerized assessment of facial hair growth. Fertil Steril 1999;72:737-9. |
| 4. | Rittmaster RS. Hirsutism [review]. Lancet 1997;349:191-5. |
| 5. | Rosenfield RL. Clinical practice. Hirsutism. N Engl J Med 2005;353:2578-88. |
| 6. | Leung AK, Robson WL. Hirsutism. Int J Dermatol 1993;32:773-7. |
| 7. | Azziz R, Carmina E, Sawaya ME. Idiopathic hirsutism. Endocr Rev 2000;21:347-62. |
| 8. | Martin KA, Chang RJ, Ehrmann DA, Ibanez L, Lobo RA, Rosenfield RL, et al. Evaluation and treatment of hirsutism in premenopausal women: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 2008;93:1105-20. |
| 9. | Gilchrist VJ, Hecht BR. A practical approach to hirsutism. Am Fam Physician 1995;52:1837-46. |
| 10. | Hunter MH, Carek PJ. Evaluation and treatment of women with hirsutism. Am Fam Physician 2003;67:65-72. |
| 11. | Lin-Su K, Nimkarn S, New MI. Congenital adrenal hyperplasia in adolescents: Diagnosis and management. Ann N Y Acad Sci 2008;1135:95-8. |
| 12. | Chang RJ, Katz SE. Diagnosis of polycystic ovary syndrome. Endocrinol Metab Clin North Am 1999;28:397-408. |
| 13. | Schmidt JB, Lindmaier A, Spona J. Hyperprolactinemia and hypophyseal hypothyroidism as cofactors in hirsutism and androgen-induced alopecia in women. Hautarzt 1991;42:168-72. |
| 14. | Wagner RF Jr. Physical methods for the management of hirsutism. Cutis 1990;45:19-26. |
| 15. | Dierickx CC. Hair removal by lasers and intense pulsed light sources. Semin Cutan Med Surg 2000;19:267-75. |
| 16. | Sanchez LA, Perez M, Azziz R. Laser hair reduction in the hirsute patient: A critical assessment. Hum Reprod Update 2002;8:169-81. |
| 17. | Battle EF Jr, Hobbs LM. Laser-assisted hair removal for darker skin types. Dermatol Ther 2004;17:177-83. |
| 18. | Burkman RT Jr. The role of oral contraceptives in the treatment of hyperandrogenic disorders. Am J Med 1995;98:130-6. |
| 19. | Shaw JC. Spironolactone in dermatological therapy. J Am Acad Dermatol 1991;24:236-43. |
| 20. | Spritzer PM, Lisboa KO, Mattiello S, Lhullier F. Spironolactone as a single agent for long-term therapy of hirsute patients. Clin Endocrinol (Oxf) 2000;52:587-94. |
| 21. | van der Spuy ZM, le Roux PA. Cyproterone acetate for hirsutism. Cochrane Database Syst Rev 2003;CD001125. |
| 22. | Faloia E, Filipponi S, Mancini V, Di Marco S, Mantero F. Effect of finasteride in idiopathic hirsutism. J Endocrinol Invest 1998;21:694-8. |
| 23. | de Leo V, Fulghesu AM, la Marca A, Morgante G, Pasqui L, Talluri B, et al. Hormonal and clinical effects of GnRH agonist alone, or in combination with a combined oral contraceptive or flutamide in women with severe hirsutism. Gynecol Endocrinol 2000;14:411-6. |
| 24. | Rittmaster RS, Loriaux DL, Cutler GB Jr. Sensitivity of cortisol and adrenal androgens to dexamethasone suppression in hirsute women. J Clin Endocrinol Metab 1985;61:462-6. |
| 25. | Emans SJ, Grace E, Woods ER, Mansfield J, Crigler JF Jr. Treatment with dexamethasone of androgen excess in adolescent patients. J Pediatr 1988;112:821-6. |
| 26. | Malhotra B, Noveck R, Behr D, Palmisano M. Percutaneous absorption and pharmacokinetics of eflornithine HCl 13.9% cream in women with unwanted facial hair. J Clin Pharmacol 2001;41:972-8. |
| 27. | Smith SR, Piacquadio DJ, Beger B, Littler C. Eflornithine cream combined with laser therapy in the management of unwanted facial hair growth in women: A randomized trial. Dermatol Surg 2006;32:1237-43. |
| 28. | Sovak M, Seligson AL, Kucerova R, Bienova M, Hajduch M, Bucek M. Fluridil, a rationally designed topical agent for androgenetic alopecia: First clinical experience. Dermatol Surg 2003;28:678-85. |
[Figure 1], [Figure 2] |
|
| This article has been cited by | | 1 |
An evaluation of the available pharmacotherapy for the treatment of hirsutism |
|
| Leila Asfour, Ahmed Kazmi, Rodney Sinclair | | Expert Opinion on Pharmacotherapy. 2023; : 1 | | [Pubmed] | [DOI] | | | 2 |
Epilation and depilation in the genital area – motivation, methods, risks and recommendations from a dermatological point of view |
|
| Evgeniia Mezin-Sarbu, Johannes Wohlrab | | JDDG: Journal der Deutschen Dermatologischen Gesellschaft. 2023; | | [Pubmed] | [DOI] | | | 3 |
Epilation und Depilation im Intimbereich – Motivation, Methoden, Risiken und Handlungsempfehlungen aus dermatologischer Sicht |
|
| Evgeniia Mezin-Sarbu, Johannes Wohlrab | | JDDG: Journal der Deutschen Dermatologischen Gesellschaft. 2023; 21(5): 455 | | [Pubmed] | [DOI] | | | 4 |
The Impact of Obesity on the Excretion of Steroid Metabolites in Boys and Girls: A Comparison with Normal-Weight Children |
|
| Marta Suminska, Rafal Podgórski, Piotr Fichna, Artur Mazur, Marta Fichna | | Nutrients. 2023; 15(7): 1734 | | [Pubmed] | [DOI] | | | 5 |
Effect of Laser-Assisted Hair Removal (LAHR) on the Quality of Life and Depression in Hirsute Females: A Single-Arm Clinical Trial |
|
| Mahboubeh Sadat Hosseini, Amir Houshang Ehsani, Yousef Fakour, Zeinab Aryanian, Mojtaba Elhamfar, Pedram Noormohammadpour | | Journal of Lasers in Medical Sciences. 2022; 13: e46 | | [Pubmed] | [DOI] | | | 6 |
The promising role of risk scoring system for Cushing syndrome: Time to reconsider current screening recommendations |
|
| CE. Lam-Chung, D. Cuevas-Ramos | | Frontiers in Endocrinology. 2022; 13 | | [Pubmed] | [DOI] | | | 7 |
Comparison of efficacy of diode laser in patients of facial hirsutism with normal dehydroepiandrosterone sulfate and dihydrotestosterone versus deranged dehydroepiandrosterone sulfate and dihydrotestosterone level—A longitudinal study |
|
| Abhishek Lachure, Nibedita Dixit, Ipsita Debata, Maitreyee Panda, Ajaya Kumar Jena, Chinmoy Raj | | Dermatologic Therapy. 2022; | | [Pubmed] | [DOI] | | | 8 |
Paraovarian Cyst Torsion in a Patient with Rubinstein-Taybi Syndrome: A Case Report |
|
| Jun Kuwabara, Satoshi Akita, Mitsunori Sato, Katsuya Watanabe, Kazufumi Tanigawa, Yusuke Matsuno, Yousuke Abe, Satoshi Kikuchi, Motohira Yoshida, Shigehiro Koga, Kei Ishimaru, Yuji Watanabe | | Journal of Nippon Medical School. 2021; 88(3): 248 | | [Pubmed] | [DOI] | | | 9 |
Clinico-investigative attributes of 122 patients with hirsutism: A 5-year retrospective study from India |
|
| Vikram K Mahajan, Pushpinder Singh Chauhan, Monika Chandel, Karaninder Singh Mehta, Vijay Karan Singh, Anuj Sharma, Reena Sharma, Jyotshna Sharma, Sheenam Hooda, Yog Raj Verma, Hitender Sharma | | International Journal of Women's Dermatology. 2021; 7(3): 237 | | [Pubmed] | [DOI] | | | 10 |
Continuum of Symptoms in Polycystic Ovary Syndrome (PCOS): Links with Sexual Behavior and Unrestricted Sociosexuality |
|
| Rebecca Tzalazidis, Kirsten A. Oinonen | | The Journal of Sex Research. 2021; 58(4): 532 | | [Pubmed] | [DOI] | | | 11 |
Is There Any Association Between Hirsutism and Serum Zinc Levels in Adolescents? |
|
| Ulvi Aliyev, Melis Pehlivantürk-Kizilkan, Yasemin Düzçeker, Nuray Kanbur, Zehra Aycan, Sinem Akgül, Orhan Derman | | Biological Trace Element Research. 2020; 198(2): 403 | | [Pubmed] | [DOI] | | | 12 |
Drug reactions affecting hair and nails |
|
| Uwe Wollina, Mohamed Badawy Abdel-Naser | | Clinics in Dermatology. 2020; 38(6): 693 | | [Pubmed] | [DOI] | | | 13 |
Mixed Form of Hirsutism in Adolescent Females and Laser Therapy |
|
| Besa Gacaferri Lumezi,Aferdita Goci,Violeta Lokaj,Hatixhe Latifi,Natyra Karahoda,Ganimete Minci,Drita Telaku,Antigona Gercari,Allma Kocinaj | | Iranian Red Crescent Medical Journal. 2014; 16(6) | | [Pubmed] | [DOI] | | | 14 |
Possible efficacy of Lavender and Tea tree oils in the treatment of young women affected by mild idiopathic hirsutism |
|
| Tirabassi, G., Giovannini, L., Paggi, F., Panin, G., Panin, F., Papa, R., Boscaro, M., Balercia, G. | | Journal of Endocrinological Investigation. 2013; 36(1): 50-54 | | [Pubmed] | | | 15 |
Triads in dermatology |
|
| Agrawal, P.G., Khopkar, U.S., Mahajan, S.A., Mishra, S.N. | | Indian Journal of Dermatology. 2013; 58(5): 346-351 | | [Pubmed] | | | 16 |
Hirsutism: Evaluation and treatment: A readeræs dilemma |
|
| Ghosh, K. | | Indian Journal of Dermatology. 2011; 56(2): 246-248 | | [Pubmed] | | | 17 |
Authoræs reply |
|
| Sachdeva, S. | | Indian Journal of Dermatology. 2011; 56(2): 248-249 | | [Pubmed] | |
|
|
|
|
|
|
|
|
|
|
|
| Article Access Statistics | | | Viewed | 19068 | | | Printed | 474 | | | Emailed | 6 | | | PDF Downloaded | 1273 | | | Comments | [Add] | | | Cited by others | 17 | | |
|
|
